A5018944263- Neurogenesis and neuroplasticity mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Mosquito-borne diseases and control
- Hereditary Neurological Disorders
- Nerve injury and regeneration
- RNA Research and Splicing
- Neuroscience and Neuropharmacology Research
- Multiple Sclerosis Research Studies
- Axon Guidance and Neuronal Signaling
- Signaling Pathways in Disease
- Viral Infections and Vectors
- RNA regulation and disease
- Mitochondrial Function and Pathology
- Fibroblast Growth Factor Research
- MicroRNA in disease regulation
- S100 Proteins and Annexins
- Virology and Viral Diseases
- Advanced Fluorescence Microscopy Techniques
- Neurological diseases and metabolism
- Alzheimer's disease research and treatments
- Genetics and Neurodevelopmental Disorders
- Advanced Neuroimaging Techniques and Applications
- Polyomavirus and related diseases
- Anesthesia and Neurotoxicity Research
- Lysosomal Storage Disorders Research
University of Glasgow
2016-2025
Max Planck Institute for Multidisciplinary Sciences
2023-2025
University of British Columbia
2024
Institute of Infection and Immunity
2023
Max Planck Institute of Experimental Medicine
2010-2022
Centre for Immunity, Infection and Evolution
2021
Hospital for Sick Children
2020
SickKids Foundation
2020
Hudson Institute
2019
Merck Institute for Science Education
2019
Axonal degeneration determines the clinical outcome of multiple sclerosis and is thought to result from exposure denuded axons immune-mediated damage. Therefore, myelin widely considered be a protective structure for in sclerosis. Myelinated also depend on oligodendrocytes, which provide metabolic structural support axonal compartment. Given that pathology already visible at early disease stages, before overt demyelination, we reasoned autoimmune inflammation may disrupt oligodendroglial...
Oligodendrocytes are critical for the development of plasma membrane and cytoskeleton axon. In this paper, we show that fast axonal transport is also dependent on oligodendrocyte. Using a mouse model hereditary spastic paraplegia type 2 due to null mutation myelin Plp gene, find progressive impairment in retrograde anterograde transport. Increased levels motor protein subunits associated with accumulation membranous organelles distal nodal complexes. cell transplantation, categorically...
Abstract Most axons in the central nervous system (CNS) are surrounded by a multilayered myelin sheath that promotes fast, saltatory conduction of electrical impulses. By insulating axon, also shields axoplasm from extracellular milieu. In CNS, oligodendrocytes provide support for long‐term maintenance myelinated axons, independent sheath. Here, we use electron microscopy and morphometric analyses to examine evolution axonal oligodendroglial changes mice deficient 2′,3′‐cyclic nucleotide...
Abstract Multiple Sclerosis (MS) is an inflammatory demyelinating disorder in which remyelination failure contributes to persistent disability. Cholesterol rate-limiting for myelin biogenesis the developing CNS; however, whether cholesterol insufficiency MS, unclear. Here, we show relationship between cholesterol, myelination and neurological parameters mouse models of demyelination remyelination. In cuprizone model, acute disease reduces serum levels that can be restored by dietary...
Demyelinating disorders of the central nervous system (CNS) occur when myelin and oligodendrocytes are damaged or lost. Remyelination regeneration can be achieved from endogenous oligodendrocyte precursor cells (OPCs) that reside in adult CNS tissue. Using a cuprizone mouse model demyelination, we show infusion fractalkine (CX3CL1) into demyelinated murine brain increases de novo formation enhances remyelination corpus callosum cortical gray matter. This is by increased OPC proliferation...
Mitochondrial dysfunction is putatively central to glioblastoma (GBM) pathophysiology but there has been no systematic analysis in GBM of the proteins which are integral mitochondrial function. Alterations enriched fractions from patients with were defined label-free liquid chromatography mass spectrometry. 256 mitochondrially-associated identified and 117 these markedly (fold-change ≥2) significantly altered (p ≤ 0.05). Proteins associated oxidative damage (including catalase, superoxide...
The recent global outbreak of Zika virus (ZIKV) infection has been linked to severe neurological disorders affecting the peripheral and central nervous systems (PNS CNS, respectively). pathobiology underlying these diverse clinical phenotypes are subject intense research; however, even principal neural cell types vulnerable productive remain poorly characterised. Here we used CNS PNS myelinating cultures from wild type Ifnar1 knockout mice examine neuronal glial tropism short-term...
Discovery of novel bacterial metabolites reveals an unprecedented role for the microbiome in gut-brain axis communication.
ABSTRACT The transcription factor Pax6 is widely expressed throughout the developing nervous system, including most alar regions of newly formed murine diencephalon. Later in embryogenesis its diencephalic expression becomes more restricted. It persists anterior thalamus (conventionally termed “ventral” thalamus) and pretectum but downregulated body posterior (dorsal) thalamus. At time this downregulation, dorsal forms major axonal efferent pathway via ventral telencephalon to cerebral...
Abstract Axonal pathology in multiple sclerosis (MS) has been described for over a century, but new insights into axonal loss and disability have refocused interest this area. There is evidence of oxidative damage to mitochondrial DNA chronic MS plaques, suggesting that failure may play role pathology. We propose the absence myelin maintenance conduction relies partially on an increase mitochondria provide energy. This increased energy requirement also promotes reactive oxygen species (ROS),...
It is widely thought that demyelination contributes to the degeneration of axons and, in combination with acute inflammatory injury, responsible for progressive axonal loss and persistent clinical disability demyelinating disease. In this study we sought characterize relationship between demyelination, inflammation transport changes using a Plp1-transgenic mouse model Pelizaeus-Merzbacher optic pathway non-immune mediated myelin progresses from nerve head towards brain, over period months....
Remyelination failure plays an important role in the pathophysiology of multiple sclerosis, but underlying cellular and molecular mechanisms remain poorly understood. We now report actively demyelinating lesions patients with sclerosis are associated increased glial expression fibroblast growth factor 9 (FGF9), which we demonstrate inhibits myelination remyelination vitro. This inhibitory activity is appearance multi-branched 'pre-myelinating' MBP+/PLP+ oligodendrocytes that interact axons...
Abstract Duplication of PLP1 , an X‐linked gene encoding the major myelin membrane protein human CNS, is most frequent cause Pelizaeus‐Merzbacher disease (PMD). Transgenic mice with extra copies wild type Plp1 gene, a valid model PMD, also develop dysmyelinating phenotype dependant on dosage. In this study we have examined effect increasing dosage levels PLP/DM20 and other representative proteins. cultured oligodendrocytes early myelinating in vivo, increased leads to elevated cell body....
Deficiency of the major constituent central nervous system (CNS) myelin, proteolipid protein (PLP), causes axonal pathology in spastic paraplegia type‐2 patients and Plp1 null ‐mice but is compatible with almost normal myelination. These observations led us to speculate that PLP's role myelination may be partly compensated for by other tetraspan proteins. Here, we demonstrate abundance structurally related tetraspanin‐2 (TSPAN2) highly increased CNS myelin ‐mice. Unexpectedly, Tspan2 ‐mutant...
Gangliosides are widely expressed sialylated glycosphingolipids with multifunctional properties in different cell types and organs. In the nervous system, they highly enriched both glial neuronal membranes. Mice lacking complex gangliosides attributable to targeted ablation of B4galnt1 gene that encodes β-1,4-N-acetylegalactosaminyltransferase 1 (GalNAc-transferase; GalNAcT(-/-)) develop normally before exhibiting an age-dependent neurodegenerative phenotype characterized by marked...